Ovarian cancer has the highest mortality among gynecological cancers. Though ovarian cancers detected in early stage are associated with a high survival (>90%), they account for less than 10% of diagnosed cancers. However, the lack of early symptoms and the absence of a reliable screening test to detect ovarian cancer result in over 70% of women being diagnosed after the disease has spread beyond the ovary so that the prognosis is poor, with approximately 12,000 deaths due to ovarian cancer annually in the United States and 114,000 deaths worldwide (5-year survival is no better than 37%). Currently, physical pelvic examination, ultrasound, or measuring blood levels for CA125 are the only standard methods available for detection of ovarian cancer. Unfortunately, none of these methods provides a reliable and accurate means to detect ovarian cancer, so it is imperative to develop novel methods for accurate detection of all ovarian cancers.

Studies have shown high levels of a protein called Bcl-2 in ovarian cancer tissue. The objective of this proposal, supported by strong preliminary data, is to determine whether Bcl-2 can be used as a novel marker for ovarian cancer. Specifically, using a simple, quantitative, commercially available ELISA assay, we plan to determine whether Bcl-2 is expressly elevated in the urine of patients with ovarian cancer so that urinary levels of Bcl-2 might be used as a new, specific, and sensitive biomarker for detection of ovarian cancer.

Initially, we will begin by optimizing urinary Bcl-2 test parameters. Then, to show specificity and sensitivity for urinary Bcl-2 to detect ovarian cancer, we will show elevated urinary Bcl-2 levels in ovarian cancer patients compared to normal healthy women, women with benign gynecologic disease, women with inflammatory disease, and patients with other types of cancer including breast, colon, endometrial, cervical, lung, bladder, melanoma, brain, and head and neck tumors. We will also measure urinary Bcl-2 levels among different types of ovarian cancers and through the course of disease as well as correlate urinary Bcl-2 with clinical parameters including ovarian tumor stage, grade, and size. Likewise, urinary Bcl-2 levels will be compared with blood CA125 levels to show improved ovarian cancer detection by urinary Bcl-2.

The experiments proposed in this application are innovative and of significant clinical relevance. Measuring urinary Bcl-2 may provide a novel, simple, safe, sensitive, specific, and economical method for the detection of ovarian cancer that would benefit all women, not only in the United States, but worldwide, including medically underserved areas and women at high risk for developing ovarian cancer. Likewise, such a simple and noninvasive screening test for ovarian cancer should result in high patient compliance. Further, urinary detection of ovarian cancer in both early and late stages of disease would not only confirm the diagnosis, but could also detect thousands of previously undiagnosed ovarian cancers contributing to improved treatment and reduced life-long medical costs. The ability to accurately detect and monitor presence of ovarian cancer throughout the course of disease using this method may also predict therapeutic and prognostic outcome. Lastly, the development of a specific test to detect ovarian cancer by levels of urinary Bcl-2 could be available to patients within a few years in stark contrast to new drug therapies that can take 10+ years before they are clinically available. The development of a new, reliable, simple, safe, and economic test to accurately detect all ovarian cancers by measuring elevated urinary Bcl-2 levels could then become the gold standard for clinical detection of ovarian cancer and would lead to improved treatment and reduced mortality of an insidious disease.